A group of researchers from ERIBA, UMCG and their international collaborators have applied a new approach: instead of searching for biomarker genes they looked into how well genes “play together”. They identify gene ensembles that are mistuned when the body encounters COVID-19 and other acute respiratory infections. Their findings are reported in the journal Scientific reports.

Among mistuned “gene ensembles”, they found increased fluctuations and noise in genes involved in mitochondrial respiration and peroxisomes across all patients with severe pneumonia, sepsis and COVID-19 symptoms. These gene ensembles are responsible for the supply of energy and the utilization of cellular waste.

For some of the affected ensembles identified in this study, drugs approved by FDA and EMA exist that help bypassing the now ill-tuned “gene ensembles in severe patients. Such drugs could be potentially affordable therapeutics in the treatment of pneumonia and sepsis caused by acute respiratory infections. Although the effectiveness of these drugs requires further investigation, this already illustrates the utility of looking for not only at solo gene players, but also at “gene ensembles”, as an alternative approach in the search for new pharmaceutical targets for the treatment of complex diseases.

Finally, the researchers showed that the new “gene ensemble” approach can be successfully applied for the prediction of clinical outcomes, namely severity and mortality, in COVID-19, pneumonia and sepsis patients. The new method represents a promising approach for the investigation of molecular mechanisms of pathology through a prism of the mistuning of genetic systems.